tbuckley/cabot-search huggingface dataset:
Robotic retroperitoneal lymph node dissection: A systematic review and meta-analysis of perioperative outcomes.
Authors: Harshit Garg, Ahmed M Mansour, Sarah P. Psutka, Simon P Kim, James Porter, Christine S Gaspard, Furkan Dursun, Deepak K Pruthi, Hanzhang Wang, Dharam Kaushik
Journal: Journal of Clinical Oncology (2023)

420 Background: Retroperitoneal lymph node dissection (RPLND) forms an integral part of the management of testis cancer. Robotic RPLND (R-RPLND) is a minimally invasive treatment option for this disease. This systematic review assessed the safety and feasibility of R-RPLND and compared the perioperative outcomes of R-RPLND with open RPLND (O-RPLND). Methods: The PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for studies reporting perioperative outcomes of primary and post-chemotherapy R-RPLND and studies comparing R-RPLND with O-RPLND. Results: The search yielded 42 articles describing R-RPLND, including five comparative studies. The systematic review included 4,224 patients (single-arm studies, n=461; comparative studies, n=3,763). Of 461 patients in the single-arm studies, 271 underwent primary R-RPLND and 190 underwent post-chemotherapy R-RPLND. For primary R-RPLND, the operative time ranged from 175-540 minutes and the major complication rate was 3.1%. For post-chemotherapy R-RPLND, the operative time ranged from 134-550 min and the major complication rate was 8.4%. The conversion rate to open surgery was 2.2% in primary R-RPLND and 8.9% in post-chemotherapy R-RPLND. In comparison with O-RPLND, R-RPLND was associated with a lower transfusion rate (14.5% vs 0.9%, p=0.0001) and a lower complication rate (18.5% vs 7.8%, p=0.002; Table). Conclusions: R-RPLND has acceptable perioperative outcomes in both the primary and post-chemotherapy settings but a notable rate of conversion to open surgery in the post-chemotherapy setting. Compared with O-RPLND, R-RPLND is associated with a lower transfusion rate and fewer overall complications. Given the potential impact of selection bias, the optimal patient selection criteria for R-RPLND remain to be elucidated. [Table: see text]
Association of mitochondrial metabolic activity and immune pathways with disease stage in renal cell carcinoma.
Authors: Shuchi Gulati, Behrouz Shamsaei, Bhargav Vemuri, Juechen Yang, Dina Secic, Megan Bischoff, Julio A Landero Figueroa, David R. Plas, Tom Cunningham, Jarek Meller, Maria F. Czyzyk-Krzeska
Journal: Journal of Clinical Oncology (2023)

722 Background: Previous large scale genomic studies have described somatic alterations that affect tumor progression. However, metabolic and immune pathway changes that occur with advancing disease stage are not well characterized. Herein, we performed transcriptomic profiling of clear-cell renal carcinoma (ccRCC) tumors across clinical stages to define these changes. Methods: TCGA Firehose Legacy cohort was used to determine differential gene expression between stage 3 ccRCCs from patients who remained disease free (S3DF) vs. those who relapsed (S3RL) within two years of nephrectomy. Single cell RNA-seq (scRNAseq) analysis was performed on primary ccRCCs from nine patients (stage 1 n=4, stage 3 n=4, metastatic n=1). Seurat V4 package and module score was used to analyze patterns of gene expression associated with tumor progression at the single cell level. Results: Transcriptomic comparison of ccRCCs from TCGA Firehose Legacy cohort revealed induction of genes encoding mitochondrial respiratory complexes and mitochondrial ribosomal proteins (MRPs) and decrease in expression of immune genes in S3RL as compared to S3DF tumors. Using a set of 23 differentially regulated mitochondrial and immune genes we established a transcriptomic signature that stratified patients into those at risk of relapse vs. not. ScRNA-seq data analysis determined increased expression of mitochondrial respiratory complexes’ gene-sets, and decreased levels of glycolytic genes and HIF targets during tumor progression from stage-I to metastatic. This was supported by spatial transcriptomics of cancer cells, which revealed clusters of cells with high mitochondrial activity and decreased MHC class I and II gene expression. Conclusions: The data support a model of progressive metabolic reprogramming from glycolysis and HIF-regulated pathways to mitochondrial respiration in parallel with diminished immune expression of antigens on cancer cells with advancing disease stage in ccRCC. Identification of targetable mitochondrial vulnerability could be a therapeutic option in patients who progress on immune checkpoint inhibitors.
Longitudinal evaluation of plasma miR371 to detect minimal residual disease and early relapse of germ cell tumors.
Authors: Lucia Nappi, Neetu Saxena, Sara Pautasso, Sylwia Mazurek, Guliz Ozgun, Catarina Kollmannsberger, Max Trottier Chi, Antoine Morin Coulombe, Maryam Soleimani, Kim N. Chi, Bernhard J. Eigl, Peter C. Black, Alan So, Martin Gleave, Sean Kern, Siamak Daneshmand, Nabil Adra, Lawrence H. Einhorn, Craig R. Nichols, Christian K. Kollmannsberger
Journal: Journal of Clinical Oncology (2023)

407 Background: Active surveillance is routinely recommended to manage patients (pts) with clinical stage I (CSI) germ cell testicular tumors (GCT), the most common presentation of newly diagnosed GCT. Circulating plasma miR371a-3p (miR371) has shown high sensitivity and specificity in pts with metastatic non teratoma GCT or in pts with clinically detectable testicular GCT prior to orchiectomy. However, limited data are available about this biomarker accuracy to detect minimal residual disease post-orchiectomy in pts on active surveillance for early stage disease. Methods: CSI GCT pts with available plasma samples after radical orchiectomy enrolled in the British Columbia provincial biobank research program were selected for this study. RT-PCR was used for qualitative miR371 analysis. Sensitivity, specificity, negative and positive predictive values (NPV, PPV) and AUC in predicting tumor recurrence were evaluated for miR371 and compared to the same operating characteristics of current gold standard diagnostic tests. Relapse free survival (RFS) was correlated to post-orchiectomy miR371 (positive or negative) status. Fisher’s exact test was used to evaluate the sensitivity and specificity, unpaired t-test for comparison of miR371 expression. RFS was calculated using the Kaplan-Meier method, and differences between groups were estimated using the log rank test, 2-sided and with 5% significance threshold. Results: With a median follow-up of 41 months, 101 pts with CSI GTCwere included, of whom 35 (34.6%) experienced a disease relapse during the follow-up. miR371 was positive in 22/35 (62.8%) of the relapsed pts. miR371 positivity preceded clinical evident disease by a median of 3 months (range: 1-12 months).The specificity and PPV were 100% (95% CI: 94.5 - 100 for both), sensitivity 62.8% (95% CI: 44.9 - 78.5), NPV 83.5% (95% CI: 76.7 - 88.6) and AUC 0.81 (95% CI: 0.71 - 0.91). No false positive results were observed. The RFS of the pts with positive post-orchiectomy miR371 was significantly shorter (median: 3.5 months vs. not reached; p&lt;0.0001) compared to the pts with a negative post-orchiectomy miR371 (HR: 16.9; 95% CI: 2.1 - 135.7; p&lt;0.0001). miR371 sensitivity correlated with tumor burden, time between tumor relapse and miRNA testing and histology (nonseminoma &gt; seminoma). Conclusions: miR371 has high specificity and PPV in detecting GCT at an early stage and could be used to guide treatment selection after orchiectomy. Further studies, including the SWOG S1823 clinical trial, are ongoing or have been planned in this setting for validation of clinical utility.
Uptake of maintenance immunotherapy and changes in upstream treatment selection in patients with advanced urothelial cancer (aUC).
Authors: Ronac Mamtani, Hanxi Zhang, Ravi Bharat Parikh, Aaron B. Cohen, Khilna Patel, Blanca Homet Moreno, Haojie Li, Kentaro Imai, Matt D. Galsky, Rebecca A. Hubbard
Journal: Journal of Clinical Oncology (2023)

466 Background: In July 2020, the FDA approved avelumab, an immune checkpoint inhibitor (ICI), for maintenance treatment of aUC that has not progressed with first-line (1L) platinum-containing chemotherapy (chemo). Availability of avelumab may have influenced upstream treatment selection between 1L chemo and 1L ICI (pembrolizumab or atezolizumab). We described avelumab use in real-world practice and determined whether 1L treatment choice changed following its approval. Methods: This cohort study used Flatiron Health’s nationwide de-identified EHR-derived database. Included patients started 1L therapy for aUC in the US before (April 1 2017 to June 30 2020) or after (July 1 2020 to May 31 2022) avelumab approval. We calculated the proportion of patients initiating 1L chemo (carboplatin- or cisplatin-based) or ICI during the pre- and post- avelumab approval periods. Time trends were estimated using multinomial logistic regression for 1L treatment choice regressed on time modeled via a natural cubic spline, allowing for a discontinuity in the time trend at the time of FDA approval. Differences in probabilities of 1L treatment in July 2020 (immediately following approval) compared to June 2020 (immediately prior to approval) were calculated. Maintenance avelumab use was described among patients treated with 1L chemo in the post-approval period, and in a sensitivity analysis, among ‘maintenance eligible’ patients defined as those who were progression-free 28 weeks after 1L chemo start. Results: Among all 1L treatment initiators (n=3,507), the FDA approval of maintenance avelumab was followed by increased use of 1L carboplatin-based chemo (+9.9%; 95% CI 1.1-17.2%) but no significant changes in the use of ICI (-5.8%; 95% CI -15.9-4.4%) or cisplatin-based chemo (-4.2%; 95% CI -12.7-5.2%) (Table). Among patients treated with 1L platinum-chemo (n=485), probability of initiating maintenance avelumab increased over time. In the 22 months after approval, approximately 20.4% (n=99/485) of all 1L chemo-treated patients and 24.3% (n=78/321) of maintenance eligible patients received maintenance avelumab. Conclusions: We found modest uptake of maintenance avelumab for aUC after FDA approval. Potential reasons include limited clinician awareness of maintenance immunotherapy and/or patient preferences against long-term treatment after response to initial chemo. Our finding of higher treatment starts with carboplatin-based chemo in the post-maintenance period suggests increasing preference by clinicians of a strategy that provides patients an opportunity for two effective treatment options. Real-world data can provide important insights on community response to regulatory approvals. [Table: see text]
Dosing, safety, and pharmacokinetics (PK) of combination therapy with darolutamide (DARO), androgen-deprivation therapy (ADT), and docetaxel (DOC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the ARASENS study.
Authors: Arash Rezazadeh, Bertrand F. Tombal, Maha H. A. Hussain, Fred Saad, Karim Fizazi, Cora N. Sternberg, E. David Crawford, Shivani Kapur, Weijiang Zhang, Bart Ploeger, Rui Li, Iris Kuss, Carsten Zieschang, Sabine Wittemer-Rump, Matthew Raymond Smith
Journal: Journal of Clinical Oncology (2023)

148 Background: In ARASENS (NCT02799602), DARO in combination with ADT and DOC significantly reduced the risk of death by 32.5% (HR 0.68; 95% CI 0.57–0.80; P&lt;0.001) vs placebo (PBO) + ADT + DOC in patients with mHSPC. Incidences of treatment-emergent adverse events (TEAEs) were similar between treatment groups. We report dosing, safety, and PK of coadministration of DARO and DOC with ADT. Methods: Patients with mHSPC were randomized 1:1 to DARO 600 mg twice daily or PBO, plus ADT and DOC (75 mg/m 2 q21d for 6 cycles). The effect of DARO on DOC PK was assessed by noncompartmental analysis from the first 25 patients with dense PK data and by population PK (PopPK) for all patients. DARO PK from ARASENS were compared with PK data from ARAMIS (NCT02200614; without DOC) to evaluate the impact of DOC on DARO PK. Results: Of 1306 randomized patients, 1305 were included in the full analysis set (DARO, n=651; PBO, n=654). The median treatment duration was longer with DARO vs PBO (41.0 vs 16.7 months) and more DARO-treated patients (45.9% vs 19.1%) were still receiving treatment at primary analysis cutoff (Oct 25, 2021). Almost all patients completed 6 cycles of DOC in both groups (DARO, 87.6%; PBO, 85.5%). The proportion of patients requiring DOC dose modification (interrupted/delayed or reduced) was similar between groups (DARO, 60.0%; PBO, 62.9%). TEAEs led to discontinuation/reduction of DOC in 8.0%/19.9% of DARO patients and 10.3%/19.5% of PBO patients. PopPK analysis indicated that DOC PK in ARASENS was generally consistent with that in the literature. A slight numeric increase in DOC exposure was observed in the DARO + DOC + ADT arm, with 15% higher maximum plasma concentration (geometric mean, 1.93 vs 1.68 µg/mL) and 6% higher area under the concentration-time curve (AUC 0-tlast within an 8-hour sampling interval, 2.10 vs 1.99 µg·h/mL) vs PBO + DOC + ADT. This small numeric increase is likely not clinically relevant given the variability in DOC exposure (coefficient of variation, 23%–54%). PK meta-analysis of ARASENS and, which considered patients’ intrinsic characteristics as covariates (eg, age, body weight, region), indicated a 10% lower AUC 0-12ss of DARO in patients receiving DOC vs those not receiving DOC, which is not considered clinically relevant. Conclusions: The combination of DARO + DOC + ADT increases overall survival with similar overall incidence of TEAEs and no observed drug-drug interactions between DARO and DOC. DARO can be effectively and safely administered with DOC in patients with mHSPC without clinically relevant changes in PK of DARO or DOC. Clinical trial information: NCT02799602 .
A comparative analysis of patients presenting with optic canal metastasis of prostate cancer.
Authors: Neil Kelkar, Jue Wang
Journal: Journal of Clinical Oncology (2023)

23 Background: Prostate cancer (PCa) is the second-most diagnosed cancer and the second leading cause of cancer deaths in United States Males. Due to an emphasis on early detection of PCa, only a small percentage present with distant disease. We report cases of ocular metastasis of PCa, a late finding of PCa. Methods: Systematic review of the literature and pooled analysis of published cases of PCa with optic canal or orbital metastasis, including one from our institution. A subgroup analysis compared those who presented with optic metastases as their initial presentation (IP) versus those who presented with optic metastases after diagnosis (AD). Results: 39 patients with ocular metastasis of PCa were selected for this study. Twenty-one cases (53%) presented with ocular metastasis in the initial presentation, and 18 presented with an optic canal metastasis after diagnosis. The overall average age was 66 years (45-85 years). The average age for the IP group was 70 years (59-85 years) and 62 years (45-70 years) for the AD group. Metastatic sites varied between cases. Nineteen cases (49%) presented with widespread lesions involving the axial skeleton, with 8 IP cases (44%) versus 11 AD cases (52%). Ten cases (26%) involved solitary metastases to the optic nerve, optic disc, choroid, or orbit, with 5 IP cases (2%) versus 5 AD cases (24%). Three cases (7.5%) presented with bilateral orbital metastases. One case (2.5%) involved bilateral solitary lesions to the optic nerves. The common complaints patients presented with were proptosis (33%), diplopia (26%), decreased visual acuity (41%), and vision loss (10.3%). Thirty-seven cases reported primary adenocarcinoma on histology (95%). Thirty cases reported mortality data, with 16 reporting patient death after diagnosis. Of these, 6 cases (out of 12) report death from PCa in the IP group, and 10 cases (out of 18) report death from PCa in the AD group. Conclusions: Despite early prostate cancer screening increases, patients can present with distant metastasis as their initial presentation. We recommend prompt tumor molecular/genetic testing to inform targeted treatment when faced with atypical cases.
Oncologists’ perspectives on metastatic hormone sensitive prostate cancer management.
Authors: Patrick Heckman, Donglin Yan, Xitong Zhou, Zin Myint
Journal: Journal of Clinical Oncology (2023)

84 Background: The treatment of metastatic hormone sensitive prostate cancer (mHSPC) has evolved over the past 7 years. Combination therapies with either [Androgen deprivation therapy (ADT) + Docetaxel] or [ADT + androgen receptor signaling inhibitors (ARSi) such as abiraterone acetate/enzalutamide/apalutamide] have demonstrated overall survival (OS) benefit compared to ADT + placebo in mHSPC. Recently two trials (ARASENS and PEACE-1) also demonstrate an OS benefit from the addition of docetaxel to ADT + ARSi (abiraterone acetate or darolutamide) compared to ADT + docetaxel. Given these recent advances there is not a clear consensus on how to best manage patients with mHSPC as there are no head-to-head trials. In this study, we assess oncologists’ treatment preferences as it pertains to this subset of patients. Methods: An 8-item online survey was sent on September 6th, 2022 to medical oncologists in the United States. We described five different case scenarios and three demographic questionnaires. Cases consisted of patients with mHSPC both de novo and primary progressive with low and high volumes. Treatment options included ADT monotherapy, ADT + ARSi (doublet), or ADT + ARSi + docetaxel (triplet therapy). Respondents reported their practice setting, location, and years of clinical experience. Data was collected and analyzed via REDCap. Results: Surveys were completed by (n=83) medical oncologists across the US. 14.5% of respondents were from Kentucky; 51.8% have been in practice &lt; 10 years, 20.5% 10-20 years, and 27.7%&gt; 20 years. For patients with de novo high volume disease, 85.5% (71) preferred treatment with triplet therapy. For the same patient population, 94.4% (51) of university-based providers preferred triplet therapy vs 68.9% (20) of those in a non-academic setting. Preferences differed regarding patients with primary progressive high-volume disease in which 59.8% (49) preferred a triplet regimen while 37.8% (31) preferred a doublet regimen. Of those choosing triplet therapy, 53.7% (29) were from an academic institution while 71.4% (20) practiced in a nonacademic setting. Of those choosing doublet therapy, 42.6% (23) were from an academic institution versus 28.6% (8) in a nonacademic setting. For patients with de novo or primary progressive low volume disease, 81.5% of respondents preferred doublet therapy without a notable difference between academic and non-academic responders. Conclusions: We find a consensus in management of patients with de novo high volume mHSPC (prefer triplet) and de novo or primary progressive low volume disease (prefer doublet) regardless of practice setting, location, or practice duration. However, for patients with primary progressive high-volume disease, a higher percentage of non-academic providers prefer triplet therapy compared to their university counterparts.
Healthcare utilization and outcomes in testicular cancer with and without HIV.
Authors: Vaishali Deenadayalan, Vinod Solipuram, Shweta Gupta
Journal: Journal of Clinical Oncology (2023)

411 Background: Risk of testicular cancer (TC) was higher in HIV patients before combined antiretroviral therapy (cART) era. However the risk has decreased and outcomes reported to be similar since cART (PMID 17548695, 34592009). We evaluated the characteristics, outcomes, and healthcare utilization of patients with TC with and without HIV from a national sample. Methods: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database was queried to identify all TC patients with and without HIV from 2016-2019. The groups were compared for socio-demographic differences, medical comorbidities, inpatient mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes included rates of orchiectomy, sepsis, septic shock, acute kidney injury, UTI, anemia, and protein energy malnutrition. Statistics were performed using t-test, univariate and multinomial logistic regression. Results: A total 265 admissions of HIV-TC and 29,450 non-HIV-TC were identified. HIV-TC patients were more likely to be in middle age group (45-65yrs) (38 vs 19% 40, p = 0.08) than non-HIV-TC who were younger &lt;45yrs (76 vs 62%, p = 0.08). Compared to non-HIV-TC, HIV-TC patients were more likely to be Black (36% vs 5%, p&lt;0.001), on Medicaid (47% vs 33%, p=0.002) or uninsured (12% vs 8%, p=0.002), treated at a teaching hospital (94% vs 84%, p=0.036). HIV-TC had a significantly higher comorbidity burden, prevalence of CKD and coinfection with Hepatitis B/C (all p&lt;0.05). Other comorbidities and secondary outcomes were not significantly different. The overall adjusted all-cause mortality was not significantly different between groups (aOR = 0.6, 95% CI 0.08-4.24, p = 0.61), however on subgroup analysis mortality was significantly increased for blacks (aOR = 1.98, 95% CI 1.07-3.66, p = 0.02) and Asians (aOR = 1.84, 95% CI 1.05-3.21, p = 0.03) compared to Caucasians. Mean LOS (7 vs 6 days, p = 0.49) and THC ($68,766 vs $69,371, p = 0.17) were similar between cohorts. Conclusions: HIV-TC patients were older, in the middle age compared to more younger (&lt;45 years) for non-HIV-TC patients. Although overall mortality and outcomes were similar between the groups, a racial disparity was seen with higher mortality in African American patients, the cause of which should be investigated in future studies.